The anaesthetic potency of the (S)-ketamine isomer is approximately double that of racemic ketamine. The aim of this study was to compare the recovery of cerebral function after a bolus of 1.3 mg/kg racemic ketamine or 0.65 mg/kg (S)-ketamine followed by continuous application of 4 or 2 mg/kg x h over 15 minutes. METHODS With their informed consent and approval of the local ethics committee 12 healthy volunteers were enrolled in a double-blind, cross-over study. All drugs were dissolved in identical volumes. On three dates with an interval of one week at least ketamine/NaCl, (S)-ketamine/physostigmine or (S)-ketamine/NaCl was administered (table 1). The sequence was randomized. In addition, the unspecific antagonistic potential of the centrally acting, cholinergic agonist physostigmine (0.012 mg/kg) after (S)-ketamine was tested against saline-placebo. Neuropsychological tests (tests 3-5 of the syndrome-short-test [Erzigkeit, see references]) were used to quantify cerebral function before and at 45, 75, 105, 135, 165 and 195 min after anaesthesia. All data are mean values and standard deviation. Comparisons over time and between drugs were carried out using two-dimensional analysis of variance (ANOVA). Wilcoxon-tests were used post-hoc. p < 0.05 was considered significant. RESULTS After (S)-ketamine the subjects were able to carry out the tasks more rapidly than after racemic ketamine (p < 0.05). Mean time to reach preoperative test performance +10% was 117.5 min for (S)-ketamine/physostigmine, 121.3 min for (S)-ketamine/NaCl and 141.6 min for racemic ketamine (p < 0.05 between (S)-ketamine and racemic ketamine). No differences were found between physostigmine and placebo. The incidence of side effects (mainly nausea, vomiting) was not different. CONCLUSIONS (S)-ketamine offers a shorter recovery time after short anaesthesia compared to racemic ketamine. The investigated dose of physostigmine was probably too low to produce antagonism of (S)-ketamine. An increased dosage of physostigmine has yet to be studied, but is likely to cause a higher rate of side effects such as nausea, vomiting, bradycardia and possibly even tonic-clonic seizures.